{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:53:27Z","timestamp":1793336007234,"version":"4.5.0"},"reference-count":145,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The joint study of cerebral asymmetries and bipolar disorder (BD) has long attracted the interest of researchers and clinicians. Nevertheless, despite the increasing awareness of hemispheric asymmetries in BD, the combined investigation of these two constructs constitutes a relatively recent area of inquiry. The main objective of the present systematic review is to systematically examine the existing literature in order to identify, integrate and critically discuss evidence of hemispheric asymmetry in BD patients in terms of brain anatomy, physiology and neuropsychological function. The initial hypotheses support the presence of atypical cerebral asymmetry and differential hemispheric activation as a function of mood states in BD. Materials and Methods: Following the collection and analysis of numerous research papers through several databases and search engines, specific papers were identified and screened according to specified inclusion and exclusion criteria. Research papers on the adult bipolar population were included, while papers including comorbidity with other disorders, lesions, or an underage or elderly population, as well as meta-analyses and reviews, were excluded. This paper aligns with the procedures in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) guidelines, and was assessed for risk of bias according to the Cochrane guidelines by the Newcastle\u2013Ottawa Scale (NOS). Results: A total of 56 papers were identified as eligible in this review. Despite inconsistent findings across the included studies, an emerging pattern suggests the presence of atypical hemispheric asymmetry in BD, both in terms of specific brain structures and functional activity. Moreover, several studies associate depressive states with increased activation of the right hemisphere, whereas manic states appear to be linked with increased activation of the left hemisphere. Conclusions: These findings support the aforementioned hypotheses and partly align with the theoretical framework of emotional laterality theories. However, although certain patterns were observed, a comprehensive understanding of functional hemispheric asymmetry in BD has not yet been achieved. The presence of contradictory findings highlights the need for further extensive and systematic research to improve understanding of this topic.<\/jats:p>","DOI":"10.3390\/medicina62040792","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:53:23Z","timestamp":1776696803000},"page":"792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hemispheric Asymmetries in Bipolar Disorder: A Systematic Review"],"prefix":"10.3390","volume":"62","author":[{"given":"Efthymia","family":"Nestora","sequence":"first","affiliation":[{"name":"Laboratory of Neuropsychology and Behavioral Neuroscience, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ioannidou","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology and Behavioral Neuroscience, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4474-7566","authenticated-orcid":false,"given":"Panayiotis","family":"Patrikelis","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology and Behavioral Neuroscience, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-7032","authenticated-orcid":false,"given":"Vasiliki","family":"Folia","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology and Behavioral Neuroscience, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","first-page":"330","article-title":"Remarks on the Seat of the Faculty of Articulated Language, Following an Observation of Aphemia (Loss of Speech)","volume":"6","author":"Broca","year":"1861","journal-title":"Bull. 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